Is Low-Dose Ponatinib of Benefit in CML After Intolerance to Other Treatments?
Posted: Wednesday, August 26, 2020
The tyrosine kinase inhibitor (TKI) ponatinib may be an effective alternative for patients with chronic myeloid leukemia (CML) whose disease has not responded to other agents. However, attention to preexisting cardiovascular conditions is necessary to limit cardiac toxicity. A recent study, conducted by Massimo Breccia, MD, of the Department of Precision and Translational Medicine, Sapienza University, Italy, and colleagues, evaluated the safety and efficacy of a reduced dosage of ponatinib in patients with CML who experienced resistance or intolerance to previous TKI therapies. Their results were published in the American Journal of Hematology.
This retrospective study looked at patients treated for CML between May 2012 and December 2019 from 14 hematologic centers in Italy. The researchers identified 52 patients who received treatment with ponatinib because they were unable to tolerate previous TKI therapies. Of the total, 38.5% of patients (n = 20) received ponatinib as second-line treatment, 44.2% of patients (n = 23) received ponatinib as third-line treatment, and 17.3% of patients (n = 9) received ponatinib as fourth-line treatment. Patient data were collected for initial dose of ponatinib; molecular response at baseline, 3, 6, and 12 months from the start of treatment; dose reductions; best achieved molecular response; and related adverse events.
The median starting dose was 22.5 mg/d (range, 15–45 mg/d). The ponatinib dosage was lowered in 40.4% (n = 21) of patients, and adverse events were reported in 46.2% (n = 24). At a reduced dosage, more than 40% of patients (n = 21) had an increase in the depth of molecular response, and molecular response improved in patients treated with 15 mg/d.
At a median follow-up of 19.2 months, the investigators noted that arterial cardiovascular adverse events were recorded in just four patients, without venous complications. However, they stressed the importance of identifying preexisting concomitant risk factors and appropriately managing patients to reduce related toxicity.
“Our results highlight the safety and efficacy of ponatinib at reduced dosage in the setting of CML patients previously intolerant to TKIs,” explained the researchers. “This treatment strategy may represent an effective option for TKI-intolerant patients,” they summarized.
Disclosure: For full disclosures of the study authors, visit onlinelibrary.wiley.com.